The role of prelimbic cortex in instrumental conditioning

Behav Brain Res. 2003 Nov 30;146(1-2):145-57. doi: 10.1016/j.bbr.2003.09.023.


Numerous studies have implicated human and primate prefrontal cortex in the ability to hold and manipulate goal or outcome-related information in working memory to guide the performance of forthcoming actions. Here we report that cell-body lesions of prelimbic cortex impair the ability of rats to select an action based on previously encoded action-outcome associations. Rats were food deprived and trained to press two levers, one delivering food pellets and the other a sucrose solution. All rats acquired the lever-press response although the initial acquisition in the prelimbic rats was significantly slower than in sham controls. Furthermore, whereas in sham-lesioned rats, post-training devaluation of one of the two outcomes using a specific satiety procedure produced a selective reduction in performance on the lever that in training delivered the prefed outcome, prelimbic rats failed to show a selective devaluation effect and appeared to reduce performance on both levers non-selectively. Importantly, this impairment only emerged in extinction; in subsequent experiments it was found that, when a specific action-outcome association was cued either by presentation of the outcome itself or by presenting a stimulus previously paired with the outcome, rats demonstrated an ability to select the associated action. These results suggest that action-outcome encoding may be intact in prelimbic rats and that the lesion impaired their ability to retain this learning in working memory in order to establish a course of action. Alternatively, the lesion may have altered the relative contribution of action-outcome and outcome-action associations to instrumental performance. On this account, prelimbic lesions affect action-outcome encoding but leave outcome-action associations intact providing the basis for outcome-mediated initiation of an action sufficient, perhaps, to support acquisition and performance in the lesioned rats.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Association Learning / drug effects
  • Association Learning / physiology*
  • Behavior, Animal
  • Conditioning, Classical
  • Conditioning, Operant / physiology*
  • Excitatory Amino Acid Agonists / toxicity
  • Extinction, Psychological / physiology*
  • Food Deprivation
  • Limbic System / anatomy & histology
  • Limbic System / drug effects
  • Limbic System / physiology*
  • Male
  • Memory / physiology
  • N-Methylaspartate / toxicity
  • Prefrontal Cortex / anatomy & histology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiology*
  • Rats
  • Rats, Long-Evans
  • Reinforcement Schedule
  • Reinforcement, Psychology*
  • Transfer, Psychology / physiology


  • Excitatory Amino Acid Agonists
  • N-Methylaspartate